The broad objective of this work is to understand the basis of formation of the ventricular chamber of the heart. This project specifically considers two distinct processes: how do cardiac muscle cells (cardiomyocytes) expand in number (proliferate), and how do coronary blood vessels form. These processes are related by virtue of being controlled by signals from the outer layer of the heart, a cell type called the epicardium. This project seeks to understand the role and mechanistic basis of these signals, primarily utilizing genetically engineered mice, explanted embryonic mouse tissue, and tissue culture cells to conduct this research. PUBLIC HEALTH RELEVANCE: Heart disease is the leading cause of death in the Western world, and is pernicious because damaged adult heart muscle is mostly not able to repair itself and regenerate. Two critical processes that would be needed for successful regeneration include the growth of cardiac muscle and the reformation of a functional vascular supply. It is widely felt that strategies based on normal processes that occur during embryonic heart development will offer the greatest likelihood for successful treatment of adult heart disease. The primary focus of this project is to address how cardiac muscle and coronary vascular formation occur in the embryo.